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. 1984 Apr;81(4):645–650. doi: 10.1111/j.1476-5381.1984.tb16130.x

Induction of hypoglycaemia and accumulation of 5-hydroxytryptamine in the liver after the injection of mitogenic substances into mice.

Y Endo
PMCID: PMC1986911  PMID: 6722393

Abstract

Various mitogenic substances (concanavalin A, pokeweed mitogen, polyI : polyC and a phorbol diester), as well as lipopolysaccharides (LPS or endotoxins), produced hypoglycaemia after being injected into mice. However, non-mitogenic immuno-stimulants (zymosan, carrageenan, an adjuvant peptide and interferon) did not induce hypoglycaemia. All of the mitogenic substances also induced an increase in 5-hydroxytryptamine (5-HT) in liver, but the non-mitogenic substances did not have this effect. The time course of the development of hypoglycaemia was similar to that of the increase in liver 5-HT. The dose-dependence of the hypoglycaemia induced by LPS was similar to that of the increase in liver 5-HT. In C3H/HeJ mice, the macrophages and/or lymphocytes of the mice are known to be less responsive to LPS, and both the LPS-induced hypoglycaemia and increase in 5-HT were less in these mice than in control mice (C3H/He and ddI mice). These results suggest that macrophages and/or lymphocytes may participate in the induction of hypoglycaemia and the increase in 5-HT induced by mitogenic substances and LPS. A possible correlation between hypoglycaemia and the increase in hepatic 5-HT is discussed, although the relationship is not substantiated.

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Selected References

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  1. Chedid L., Audibert F., Johnson A. G. Biological activities of muramyl dipeptide, a synthetic glycopeptide analogous to bacterial immunoregulating agents. Prog Allergy. 1978;25:63–105. [PubMed] [Google Scholar]
  2. Endo Y. A lipopolysaccharide and concanavalin A induce variations of serotonin levels in mouse tissues. Eur J Pharmacol. 1983 Aug 5;91(4):493–499. doi: 10.1016/0014-2999(83)90175-9. [DOI] [PubMed] [Google Scholar]
  3. Filkins J. P., Cornell R. P. Depression of hepatic gluconeogenesis and the hypoglycemia of endotoxin shock. Am J Physiol. 1974 Oct;227(4):778–781. doi: 10.1152/ajplegacy.1974.227.4.778. [DOI] [PubMed] [Google Scholar]
  4. Filkins J. P. Endotoxin-enhanced secretion of macrophage insulin-like activity. J Reticuloendothel Soc. 1980 May;27(5):507–511. [PubMed] [Google Scholar]
  5. Furman B. L. The hypoglycaemic effect of 5-hydroxytryptophan. Br J Pharmacol. 1974 Apr;50(4):575–580. doi: 10.1111/j.1476-5381.1974.tb08591.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Glode L. M., Scher I., Osborne B., Rosenstreich D. L. Cellular mechanism of endotoxin unresponsiveness in C3H/HeJ mice. J Immunol. 1976 Feb;116(2):454–461. [PubMed] [Google Scholar]
  7. Goodrum K. J., Berry L. J. The use of Reuber hepatoma cells for the study of a lipopolysaccharide-induced macrophage factor: glucocorticoid-antagonizing factor. Lab Invest. 1979 Aug;41(2):174–181. [PubMed] [Google Scholar]
  8. Greaves M., Janossy G. Elicitation of selective T and B lymphocyte responses by cell surface binding ligands. Transplant Rev. 1972;11:87–130. doi: 10.1111/j.1600-065x.1972.tb00047.x. [DOI] [PubMed] [Google Scholar]
  9. Humes J. L., Bonney R. J., Pelus L., Dahlgren M. E., Sadowski S. J., Kuehl F. A., Jr, Davies P. Macrophages synthesis and release prostaglandins in response to inflammatory stimuli. Nature. 1977 Sep 8;269(5624):149–151. doi: 10.1038/269149a0. [DOI] [PubMed] [Google Scholar]
  10. Keightley R. G., Cooper M. D., Lawton A. R. The T cell dependence of B cell differentiation induced by pokeweed mitogen. J Immunol. 1976 Nov;117(5 Pt 1):1538–1544. [PubMed] [Google Scholar]
  11. Lloyd P., Stribling D., Pogson C. I. Endotoxin and tryptophan-induced hypoglycaemia in rats. Biochem Pharmacol. 1982 Nov 15;31(22):3571–3576. doi: 10.1016/0006-2952(82)90577-9. [DOI] [PubMed] [Google Scholar]
  12. Nagel J. E., Chrest F. J., Adler W. H. Mitogenic activity of 12-O-tetradecanoyl phorbol-13-acetate on peripheral blood lymphocytes from young and aged adults. Clin Exp Immunol. 1982 Jul;49(1):217–224. [PMC free article] [PubMed] [Google Scholar]
  13. Nowakowski M., Edelson P. J., Bianco C. Activation of C3H/HeJ macrophages by endotoxin. J Immunol. 1980 Nov;125(5):2189–2194. [PubMed] [Google Scholar]
  14. Rosenstreich D. L., Farrar J. J., Dougherty S. Absolute macrophage dependency of T lymphocyte activation by mitogens. J Immunol. 1976 Jan;116(1):131–139. [PubMed] [Google Scholar]
  15. Rosenstreich D. L., Mizel S. B. The participation of macrophages and macrophage cell lines in the activation of T lymphocytes by mitogens. Immunol Rev. 1978;40:102–135. doi: 10.1111/j.1600-065x.1978.tb00403.x. [DOI] [PubMed] [Google Scholar]
  16. Ryan J. L., Glode L. M., Rosenstreich D. L. Lack of responsiveness of C3H/HeJ macrophages to lipopolysaccharide: the cellular basis of LPS-stimulated metabolism. J Immunol. 1979 Mar;122(3):932–935. [PubMed] [Google Scholar]
  17. Scher I., Strong D. M., Ahmed A., Knudsen R. C., Sell K. W. Specific murine B-cell activation by synthetic single-and double-stranded polynucleotides. J Exp Med. 1973 Dec 1;138(6):1545–1563. doi: 10.1084/jem.138.6.1545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Smith S. A., Carr F. P., Pogson C. I. The metabolism of L-tryptophan by isolated rat liver cells. Quantification of the relative importance of, and the effect of nutritional status on, the individual pathways of tryptophan metabolism. Biochem J. 1980 Nov 15;192(2):673–686. doi: 10.1042/bj1920673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Smith S. A., Elliott K. R., Pogson C. I. Inhibition of hepatic gluconeogenesis by tryptophan metabolites in rats and guinea pigs. Biochem Pharmacol. 1979 Jul 15;28(14):2145–2148. doi: 10.1016/0006-2952(79)90196-5. [DOI] [PubMed] [Google Scholar]
  20. Smith S. A., Pogson C. L. Tryptophan and the control of plasma glucose concentrations in the rat. Biochem J. 1977 Dec 15;168(3):495–506. doi: 10.1042/bj1680495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sugio K., Tsurufuji S. Mechanism of anti-inflammatory action of glucocorticoids: re-evaluation of vascular constriction hypothesis. Br J Pharmacol. 1981 Jul;73(3):605–608. doi: 10.1111/j.1476-5381.1981.tb16794.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Tadano T., Endo Y., Kisara K. A simple determination of serotonin, 5-hydroxyindoleacetic acid and 5-hydroxytryptophan decarboxylase activity in rat brain areas and parallel correlation among the levels. Jpn J Pharmacol. 1980 Jun;30(3):347–356. doi: 10.1254/jjp.30.347. [DOI] [PubMed] [Google Scholar]
  23. UDENFRIEND S., WEISSBACH H., BOGDANSKI D. F. Increase in tissue serotonin following administration of its precursor 5-hydroxytryptophan. J Biol Chem. 1957 Feb;224(2):803–810. [PubMed] [Google Scholar]
  24. Vignaux F., Gresser I. Hypoglycemia in mice injected with interferon inducers is not mediated by interferon. Infect Immun. 1981 Aug;33(2):331–337. doi: 10.1128/iai.33.2.331-337.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wilson G. A., Furman B. L. Effects of inhibitors of 5-hydroxytryptamine uptake on plasma glucose and their interaction with 5-hydroxytryptophan in producing hypoglycaemia in mice. Eur J Pharmacol. 1982 Mar 12;78(3):263–270. doi: 10.1016/0014-2999(82)90027-9. [DOI] [PubMed] [Google Scholar]
  26. Witek-Janusek L., Filkins J. P. Insulin-like action of endotoxin: antagonism by steroidal and nonsteroidal anti-inflammatory agents. Circ Shock. 1981;8(5):573–583. [PubMed] [Google Scholar]
  27. Wolfe R. R., Elahi D., Spitzer J. J. Glucose and lactate kinetics after endotoxin administration in dogs. Am J Physiol. 1977 Feb;232(2):E180–E185. doi: 10.1152/ajpendo.1977.232.2.E180. [DOI] [PubMed] [Google Scholar]
  28. Yelich M. R., Filkins J. P. Mechanism of hyperinsulinemia in endotoxicosis. Am J Physiol. 1980 Aug;239(2):E156–E161. doi: 10.1152/ajpendo.1980.239.2.E156. [DOI] [PubMed] [Google Scholar]

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